Anemias

What hemoglobin level defines anemia in females?

Hemoglobin <12 g/dL

What hemoglobin level defines anemia in males?

Hemoglobin <13.6 g/dL

What hematocrit defines anemia in females?

Hematocrit <36%

What hematocrit defines anemia in males?

Hematocrit <41%

What are the 3 major causes of anemia?

Decreased RBC production, Increased RBC destruction (hemolysis), Increased RBC loss

What is intravascular hemolysis?

RBC destruction within blood vessels

What happens to haptoglobin in intravascular hemolysis?

Decreases because it binds free hemoglobin

What RBC abnormality is associated with intravascular hemolysis?

Schistocytes

What urine finding may occur with intravascular hemolysis?

Hemoglobinuria

What is extravascular hemolysis?

RBC destruction in the spleen and liver

What RBC abnormality is associated with extravascular hemolysis?

Spherocytes

Why does iron deficiency usually not occur in extravascular hemolysis?

Iron is recycled and stored after RBC destruction

Common physical exam findings in hemolytic anemia?

Pallor, jaundice, splenomegaly

Why is MCV often elevated in hemolytic anemia?

Increased reticulocytes are larger than mature RBCs

Typical reticulocyte count in hemolytic anemia?

Increased

Typical bilirubin level in hemolytic anemia?

Increased (especially unconjugated)

Typical LDH level in hemolytic anemia?

Increased

Typical haptoglobin level in intravascular hemolysis?

Decreased

Major categories of hemolytic anemia causes?

Structural defects, hemoglobinopathies, metabolic defects, immune-related disorders

What is the cause of hereditary spherocytosis?

Inherited defect in RBC membrane proteins causing spherical RBCs

What is the inheritance pattern of hereditary spherocytosis?

Usually autosomal dominant

What is the pathophysiology of hereditary spherocytosis?

Spherocytes become trapped in splenic red pulp and undergo extravascular hemolysis

What is a peripheral smear finding in hereditary spherocytosis?

Spherocytes

What is the classic presentation of hereditary spherocytosis?

Anemia, jaundice, splenomegaly

Why are gallstones common in hereditary spherocytosis?

Chronic bilirubin production from hemolysis

What is the hemoglobin level in hereditary spherocytosis?

Variable decrease

What is the reticulocyte count in hereditary spherocytosis?

Increased

What is the MCV in hereditary spherocytosis?

Usually normal, sometimes low

What is the MCHC finding in hereditary spherocytosis?

Increased

What is one of the few causes of increased MCHC?

Hereditary spherocytosis

What is the Coombs test result in hereditary spherocytosis?

Negative

What are the diagnostic tests for hereditary spherocytosis?

Osmotic fragility test, EMA binding test, ektacytometry

What is the treatment for hereditary spherocytosis?

Folic acid supplementation

What is the definitive treatment for hereditary spherocytosis?

Splenectomy

Why are iron supplements usually not needed in hereditary spherocytosis?

Iron is recycled from destroyed RBCs so excess could lead to iron overload

What is the cause of alpha thalassemia?

Alpha-globin gene deletions

What is the pathophysiology of alpha thalassemia?

Reduced alpha-chain production causes excess beta chains that damage RBC membranes

Which populations are most commonly affected by alpha thalassemia?

Southeast Asian and Chinese populations

What are the peripheral smear findings in alpha thalassemia trait?

Microcytosis, hypochromia, target cells

What are the peripheral smear findings in Hemoglobin H disease?

Microcytosis, hypochromia, target cells, poikilocytosis

What are the peripheral smear findings in hydrops fetalis?

Microcytic misshapen RBCs and nucleated erythroid precursors

What is the MCV in alpha thalassemia?

Markedly decreased

What is the RBC count in alpha thalassemia?

Increased

What is the hemoglobin electrophoresis finding in HbH disease?

HbH band present

What inclusion bodies may be seen in HbH disease?

HbH inclusion bodies

What is the treatment for an alpha thalassemia silent carrier?

None; genetic counseling

What is the treatment for alpha thalassemia trait?

Usually none; genetic counseling

What is the treatment for Hemoglobin H disease?

Folic acid, avoid oxidative drugs, transfusions if needed

What is the definitive outcome of hydrops fetalis?

Usually fatal in utero

What is the cause of beta thalassemia?

Beta-globin gene point mutations

What is Beta+ thalassemia?

Reduced beta-chain synthesis

What is Beta0 thalassemia?

Absent beta-chain synthesis

What are the hemoglobin electrophoresis findings in beta thalassemia?

Increased HbA2 and HbF

What is the pathophysiology of beta thalassemia?

Excess alpha chains precipitate and damage RBC membranes

What are the peripheral smear findings in beta-thalassemia minor?

Microcytosis, hypochromia, target cells

What are the peripheral smear findings in beta-thalassemia major?

Microcytosis, hypochromia, target cells, poikilocytosis, nucleated RBCs

What is the classic facial finding in severe beta-thalassemia?

Chipmunk facies

What is the MCV in beta thalassemia?

Markedly decreased

What is the RBC count in beta thalassemia?

Increased

What is the definitive treatment for beta-thalassemia major?

Allogeneic bone marrow transplant

What medication promotes RBC production in transfusion-dependent beta thalassemia?

Luspatercept (Reblozyl)

What is the most common demographic affected by beta thalassemia?

Mediterranean populations

What is the cause of sickle cell disease?

Autosomal recessive mutation causing HbS formation

What is the pathophysiology of sickle cell disease?

HbS polymerizes causing RBC sickling, vaso-occlusion, and hemolysis

What causes vaso-occlusive crises in sickle cell disease?

Rigid sickled RBCs obstructing microcirculation

What are the peripheral smear findings in sickle cell disease?

Sickled cells, target cells, Howell-Jolly bodies

Why are Howell-Jolly bodies seen in sickle cell disease?

Functional asplenia

What are the classic symptoms of sickle cell disease?

Pain crises, jaundice, anemia, dactylitis

What are common locations of pain crises in sickle cell disease?

Bones, joints, abdomen, soft tissues

What is the reticulocyte count in sickle cell disease?

Increased

What is the MCV in sickle cell disease?

Usually normal

What is the diagnostic test for sickle cell disease?

Hemoglobin electrophoresis showing HbS

What is the mainstay disease-modifying therapy for sickle cell disease?

Hydroxyurea

How does hydroxyurea work in sickle cell disease?

Increases HbF production

What is a major side effect of hydroxyurea?

Bone marrow suppression

What monoclonal antibody is used in sickle cell disease?

Crizanlizumab

What is an alternative medication when hydroxyurea cannot be tolerated?

L-glutamine (Endari)

What is the acute sickle cell crisis treatment mnemonic?

HOP = Hydration, Oxygenation, Pain control

What is the definitive treatment for sickle cell disease?

Allogeneic hematopoietic stem cell transplant

What are common triggers of sickle cell crisis?

Hypoxia, acidosis, infection, dehydration, exercise, temperature changes, stress

What is the inheritance pattern of G6PD deficiency?

X-linked recessive, more common in males

What is the function of G6PD?

Protects RBCs from oxidative stress

What is the pathophysiology of G6PD deficiency?

Oxidative stress causes Heinz body formation and RBC destruction either by the spleen (extravascular) or spontaneously (instravascular)

What are the peripheral smear findings in G6PD deficiency?

Bite cells, blister cells, reticulocytes

What stain demonstrates Heinz bodies?

Special supravital stain

What are three major triggers of G6PD hemolysis?

Infection, fava beans, medications

What are examples of medications that trigger G6PD hemolysis?

Sulfa drugs, quinolones, nitrofurantoin, aspirin, phenazopyridine

What are the symptoms of acute G6PD hemolysis?

Jaundice, dark urine, weakness, abdominal or back pain

What is the MCV in G6PD deficiency?

Normal

What is the diagnostic test for G6PD deficiency?

G6PD enzyme assay

What is the treatment of G6PD deficiency?

Avoid triggers, folic acid, supportive care

What is the most common enzyme deficiency worldwide?

G6PD deficiency

What is the cause of autoimmune hemolytic anemia (AIHA)?

Autoantibodies (usually IgG) form against RBC surface antigens

What percentage of AIHA cases are idiopathic?

~50%

What diseases are associated with AIHA?

SLE, CLL, lymphoma

What common drugs are associated with drug-induced immune hemolytic anemia?

Penicillins, cephalosporins, quinolones, methyldopa, levodopa, NSAIDs

What is the pathophysiology of AIHA?

Antibodies tag RBCs for destruction by the immune system

How are spherocytes formed in AIHA?

Splenic macrophages partially remove RBC membranes

What type of hemolysis is primarily seen in AIHA?

Primarily extravascular hemolysis

Can AIHA cause intravascular hemolysis?

Yes, especially IgM-mediated complement activation